Because of the introduction of new processing parameters in water-assisted injection molding (WAIM), processes control has become more difficult. First, design of experiment (DOE) was carried out by using optimized Latin hypercubes (Opt LHS). On the basis of this, computational fluid dynamics (CFD) method was used to simulate and calculate hollowed core ratios and wall thickness differences of cooling water pipe at different positions. Then inverse radial basis function (RBF) neural network model reflecting the fitting relationship between processing parameters and molding quality was established, and accuracy of the model was detected by cross validation. Finally, expected molding quality was applied to predict processing parameters, and the obtained molding quality under the predicted processing parameters was verified by computer aided engineering (CAE) simulation and experimental methods. The results showed that mean relative precisions of processing parameters such as melt temperature, delay time, short shot size, water pressure, and mold temperature for inverse RBF model were 98.6%, 93.6%, 98.5%, 93.9%, and 97.9%, respectively, which met the accuracy requirements. Furthermore, compared with expected values of hollowed core ratios and wall thickness differences, the average errors of CAE and experiment were 2.3% and 4.9%, respectively.